The etiology of the so-called chronic prostatitis is uncertain in over 90% of men diagnosed, and therapy is largely empirical and ineffective. The long-term objectives of this proposal are to determine the causes, consequences, and optimal therapy for chronic prostatitis syndromes (CPS). The specific aims are: (1) Test the hypothesis that genitourinary tract infection is important using clinical, microbiological, and molecular approaches. Preliminary studies used polymerase chain reaction (PCR) methods to identify microbial DNAs in patients with CPS (25% by one and 77% by another assay) and found that such patients were more likely to have inflammation in their expressed prostatic secretions (EPS). These observations will be extended and it will be determined if the spectrum of organisms associated with chronic inflammatory prostatitis differs from the spectrum of organisms associated with non-inflammatory prostatitis. (2) Test the hypothesis that multiple EPS evaluations are needed for accurate patient classification. The new NIH classification distinguishes patients with EPS inflammation from those without inflammation. Preliminary data suggest that some patients have intermittent EPS inflammation. This study will establish if patients need multiple evaluations of their EPS and provide insight into the sources and characteristics of leukocytes in the prostatic secretions. (3) Test the hypothesis that men with CPS and EPS or seminal inflammation are more likely to have abnormal prostatic blood flow than patients without inflammation. Preliminary studies established methods to evaluate leukocytes in EPS, seminal fluid and prostatic parenchyma, and to measure the amount and distribution of blood flow within the prostate. This study will provide insight into the pathophysiology of chronic prostatitis and establish the clinical utility of these evaluations. (4) Test the hypothesis that patients with EPS inflammation are more likely to exhibit bladder stigmata associated with interstitial cystitis than patients with EPS inflammation. Preliminary data suggest that some patients exhibit petechial bladder hemorrhages and glomerulations after hydrodistension. This study will provide insight into the pathophysiology of chronic prostatitis and the clinical utility of cystoscopy under anaesthesia for evaluating patients.